T he perception of pain involves a stimulus, which may be physical (eg, electrical current, pressure) or chemical (eg, inflammatory proteins), detection of the stimulus by receptors called nociceptors, transmission of the stimulus via of the nerves, and interpretation of the stimulus in the brain. Nociceptive pain is an inflammatory response to tissue damage with an identified trigger or stimulus. Usually, relatively acute, nociceptive pain resolves when the tissue damage stops and the inflammation subsides. In contrast, persistent injury to the peripheral or central nerves themselves produces a pain that tends to be more chronic and is referred to as neuropathic pain.1 Neuropathic pain is independent of acute stimuli or triggers. Often, it is described as tingling or stinging and when more severe, as stabbing or shooting. Alternatively, the local area may be warm or have sudden unpredictable "jumping" or electric shock-like sensations. With persistent tissue injury and inflammation, the peripheral pain-sensing nerves, as well as responses in the central nervous system, become sensitized. Increased sensitivity of neurons to a repeated stimulus can cause benign sensations to become painful (allodynia). In addition, a secondary increase in surrounding uninjured skin sensitivity to any stimulation (eg, slightly stroking the skin) may occur.1 The central nervous system itself may become sensitized as a result of neurotransmitter substance P and excitatory amino acids.2,3 The regeneration of severed peripheral nerves as with amputation also may result in increased frequency of signals sent to the spinal cord. Spontaneous impulses may be generated, resulting in pain occurring with normally benign stimuli.1 In summary, trauma to the peripheral nerves often is associated with abnormal sensory function and a marked increase in patients' response to pain. The term chronic pain has been used extensively in the medical literature and has an unfortunate inference as a negative term associated with futility of treatment or drug-seeking behavior. The term persistent pain may encourage a more positive attitude by patients and health professionals.4 Wound Pain The Krasner model5 divides chronic wound pain into the following three categories: 1. Noncyclic acute wound pain occurs during intermittent manipulation of the wound, such as with debridement. Use of local anesthesia, adequate preparation of the patient, and premedication can help reduce this pain. 2. Cyclic acute wound pain accompanies regular procedures, such as dressing changes and patient repositioning. In addition to the previous strategies, use of nontraumatic dressings, soaking dressings before removal, and allowing patient control can minimize this type of pain. 3. Chronic wound pain is the persistent pain that the patient feels all the time, even when the wound is not being manipulated. Both non-pharmacologic and pharmacologic treatments can be used. Pain signals that are associated with tissue injury have an important function and are clinically important symptoms to acknowledge. For example, pain or any change in pain is a key predictor of wound infection and is also one of the four cardinal signs for inflammation. Pain or the fear of pain also can influence the healing process by interfering with the immune response. Unresolved pain is often associated with delayed wound closure. The following important points should be heeded regarding pain management as it relates to wounds: * Analgesics can have a negative impact on healing. * Anti-inflammatory agents (NSAIDS) may reduce pain but may affect wound healing. * Antidepressant or antiepileptic agents raise questions regarding the tissue repair processes. Before clinicians consider treatment with analgesics or other treatment modalities, the source of pain should be thoroughly investigated and only interventions that will alleviate the real or potential injury to tissue should be initiated. Pain Assessment A thorough pain history is essential to wound pain management. The nature, onset, duration, and exacerbating and relieving factors will help determine the cause of the pain and direct strategies for relief. Nociceptive pain often is described as aching or throbbing; whereas, neuropathic pain may be described as burning, lancinating or electric shock like. Pain intensity can be reliably measured using validated pain scales. Several pain scales (see Figure 1) have been widely accepted for use among older adults, including people with mild to moderate cognitive impairment. A verbally administered 0 to 10 scale is a good first choice for measuring pain intensity. If the patient has difficulty with the scale, other verbal descriptor scales, pain thermometers, and faces pain scales also have accepted validity and reliability in this population.4 The scale of choice should be appropriate for the individual and used consistently with each assessment.6 Although sensory and cognitive impairment may be present, pain can usually be assessed accurately using techniques adapted for the individual's disabilities.7,8 Older patients may make pain assessment challenging.14,15 Many patients and their families accept pain as an inevitable consequence of aging, do not believe pain can be treated, may fear diagnostic tests, and/or assign too much importance to hypothetical medication side-effects or addiction.4 A patient with severe dementia who suffers from pain presents a particular challenge. In this case (or in the case of a nonverbal patient) pain can be assessed by directly observing the patient or obtaining a history from caregivers. Patients should be observed for evidence of pain-related behaviors during movement or dressing changes. Deteriorating cognitive status or agitation also should elicit assessment for pain as a potential cause.4 Whether the presence of dementia affects the experience of pain is not known.16 Therapeutic experience dictates that clinicians should have a high index of suspicion regarding pain when people with cognitive impairment have diseases associated with significant pain (chronic wounds, arthritis, ischemia, cancer). Patients with persistent pain should be reassessed regularly for improvement, deterioration, or adherence to medication regimens. The use of a pain diary with entries regarding pain intensity, medications used, mood, and response to treatment may be a good management strategy.4 Many barriers exist to optimal pain management (see Table 1). Pain Management The management of wound pain can be integrated into the wound management paradigm19: treat the cause and address local wound factors and patient-centered concerns (see Figure 2). Treating the cause should determine the correct diagnosis and initiate treatment of the wound pain. Patient-centered concerns must focus on what the patient sees as the primary reasons and resolutions for the pain. Patient anticipatory pain and suffering can be just as disruptive to quality of life as the actual experience of pain. Local wound care needs to revolve around the three pillars of local wound care practice: debridement, bacterial balance/prolonged inflammation, and moisture balance. The Krasner model emphasizes the timing of wound pain to identify the appropriate trigger and plan treatment. Treat the cause. Treating the cause of chronic wound pain may involve removing the source of the noxious stimulus - for example, reducing pressure in pressure ulcers and initiating strategies to increase arterial flow in ischemic ulcers may help reduce related chronic wound pain. Eliminating bacterial infection will remove the bacteria that stimulate ongoing inflammation. If the inflammatory stimulus cannot be reduced or removed, strategies to block peripheral nociceptors, reduce the irritability of the peripheral nerves, or block pain perception in the central nervous system should be employed. These pharmacological interventions are most effective when coupled with non-pharmacologic interventions that acknowledge patient-centered concerns.20,21 Pharmacological management. The most common approach to pain management is use of analgesic medications. However, these interventions must be used with care in older patients. Older patients have been systematically excluded from clinical trials of these drugs. In 83 randomized controlled trials of nonsteroidal anti-inflammatory drugs (NSAIDS) that included almost 10,000 patients, only 2.3% were aged 65 years or older and none were age 85 years or older.22 Older patients are generally more susceptible to adverse drug reactions. Starting with a low dose, frequent monitoring, and titrating as needed will help ensure a low level of adverse effects. This process may take 1 to 2 days for some short-acting drugs and up to 1 week for longer-acting medications. Individually adapted therapeutic adjustments are characteristic of effective pharmacotherapy for persistent pain. For health practitioners or patients to expect complete absence of pain in some cases is unrealistic.4 The World Health Organization ladder23,24 is a pharmacological approach to pain, classifying pain as mild, moderate, or severe (see Figure 3). Mild, nociceptive pain is best treated with mild analgesics, while moderate to severe pain may be treated with increasing strengths of narcotic agents. Neuropathic pain (due to nerve irritation) is often accompanied by burning and stinging and may be best treated with tricyclic anti-depressants.25 Stabbing or shooting pain indicates more intense nerve irritation or damage; anti-epileptic agents (eg, gabapentin) have been demonstrated to be therapeutically beneficial.26 Non-opioids. Most patients with persistent mild to moderate musculoskeletal pain respond favorably to around-the-clock doses of acetaminophen. The maximum dose for patients with normal renal and hepatic function and no history of alcohol abuse is 4,000 mg per day.27 When maximum safe doses of acetaminophen do not adequately control pain, NSAID therapy may be helpful.28-30 In frail older patients with multiple system disease, the persistent use of traditional NSAIDs is associated with an unacceptable rate of life-threatening gastrointestinal bleeding.28,31 The combined use of acetaminophen and NSAIDS is unlikely to enhance pain relief.4 The cyclo-oxygenase (COX)-2 selective drugs may be safer than non-selective COX inhibitors in terms of gastrointestinal morbidity and antiplatelet effects; COX-2 inhibitors, like traditional NSAIDS, may have renal or cardiovascular adverse effects (see Table 2). In addition, drug-to-drug interactions associated with COX-2 inhibitors remain a continuing area of investigation. In the end, the chronic use of opioids for persistent pain or some other analgesic strategies may have fewer life-threatening risks than the long-term daily use of high-dose, non-selective NSAIDS.31 Opioids. The use of opioid analgesic drugs for persistent non-cancer related pain remains controversial. However, consensus statements from major professional pain organizations (eg, the Canadian Pain Society, the American Academy of Pain Management, and the American Pain Society) endorse their use in appropriate situations, and the practice is becoming more acceptable.4 Although healthcare providers have been reluctant to prescribe these drugs because of political and social pressures, the incidence of addictive behavior among patients taking opioid drugs for medical reasons is low.32-35 Consultation with a specialist in pain medicine may be needed, but unfortunately these consultants are not always available on a timely basis to primary care physicians. Therefore, a consultation with a specialist in pain management should not be a prerequisite to the use of opioid therapy.36 Opioid peak concentrations occur 60 to 90 minutes after oral ingestion. When given as breakthrough doses for dressing changes, these drugs should be given in the appropriate time frame to be effective (see Table 3). Long-term opioid therapy should be started at low doses and carefully titrated until an adequate level of analgesia is obtained or until unmanageable side effects occur. Use of combination products (eg, oxycocet [Oxycet, Technilab, Quebec, Canada, or Percocet, Dupont Pharma, Ontario, Canada]) may be limited because of ceiling doses of acetaminophen or acetylsalicylic acid (ASA) which are combined with the opioid. In addition, these combination medications often contain caffeine as a co-analgesic and may be undesirable in some patients. Use of an opioid with a long duration of action has many advantages for treating chronic pain: It can facilitate patient adherence and provide a more consistent blood level (hence, fewer side effects).37 Breakthrough opioid doses should be provided and may be used, for example, before dressing changes. The goal of optimal opioid titration is to decrease the frequency of breakthrough doses to a minimum.36 Methadone is a potent µ-opioid-receptor agonist. It can be an effective medication for treatment of chronic pain and may slow the development of opioid tolerance. However, it is difficult to titrate because of its long and variable half-life.38 Clinicians prescribing methadone must be experienced with its use in closely monitored settings.39 In some jurisdictions, methadone prescription is limited to specifically authorized physicians who prescribe it primarily for the treatment of drug habituation (see Table 4). Monitoring side effects of opioid therapy should focus on neurologic, gastrointestinal, and cognitive-behavioral effects. Common side effects should be anticipated and prevented before they become severe problems. A prophylactic bowel regimen should be initiated with the commencement of persistent opioid therapy. Adjuvant drugs. A number of drugs developed for purposes other than analgesic may alter or modulate pain perception. Selective serotonin-reuptake inhibitors (SSRI) have improved the treatment of depression, but have not been effective against pain. Amitriptyline, nortriptyline, desipramine (all antidepressants) and gabapentin (an anti-epileptic) may be considered alternatives but should be used with caution in the elderly as they may cause unacceptable side effects. Drugs to avoid. Meperidine should be avoided in treating chronic pain, particularly in the elderly patient, because of the increased risk for seizures. It is best used in the short term for acute pain. Other drugs that are also not recommended include pentazocine.16 Patient-Centered Concerns in Wound Care Pain in the context of wound care often has been described as the patient's subjective experience. However, more often than not, it is the caregiver who interprets patient pain according to his/her own cultural/environmental perspective. Pain management in wound care is still a "shifting sands" of theories and practices that appear to often leave the individual experiencing the pain with little real solace. Although "pain management experts" are available, patients in pain are frequently at the mercy of less well-informed members of the healthcare team whose approach can range from feast (the more pain medication the better) to famine (limiting pain medication because of fears of addictive or drug-seeking behaviors). In addition, the pain experience of the elderly (who make up the majority of wound care patients) is often marginalized and poorly controlled. A survey study was conducted in the United Kingdom40 to explore the knowledge base and attitudes of wound care providers regarding the issues of pain and trauma in wound care. Based on the results of this study, an international survey was conducted in 10 additional countries across Europe and North America; 3,918 wound care providers responded. Summary data is presented in the European Wound Management Association position document.41 Although more than half of the respondents identified pain/trauma relief as main considerations in wound dressing changes, in many countries (eg, Canada and the US) approximately half the respondents were unaware of wound care products designed specifically to deal with pain/trauma. It seems evident that wound care providers would benefit from education on the pathophysiology of wounds and wound pain, assessment tools, and treatment options to decrease pain/trauma at dressing change. In addition, the gap in patient-centered wound care management strategies needs further research in order to create an environment where pain and trauma are diminished or eradicated when possible. Barriers to effective pain management. A patient-centered approach to pain management in wound care requires the recognition of pain as a problem related not only to somatic factors, but also to the numerous other factors that affect an individual's psychological state. The attitude, beliefs, and knowledge-base of caregiver and patient/family must be explored because these form the basis for action/inaction surrounding pain management in wound care.42 For example, treating the wound as separate from the whole person leads to a view of the wound dressing as a task to be completed rather than a biopsychosocial experience of the patient. This mechanistic, functional approach blocks the care provider from understanding this experience from the patient's perspective and from effecting appropriate care. Frequently, caregivers and patients lack knowledge and information regarding the pathophysiology of wounds and wound healing and are unaware of treatments (eg, dressings, medications) that can decrease pain and trauma at dressing change. Opportunities to learn evidence-based approaches to wound healing, including dressing and medication options, are required. The information needs to be shared with patients and families in "user friendly" language. Activating a patient-centered approach to wound care. To ensure practice is patient-centered, care decisions should be based on the following tenets: 1. Recognize the intrinsic value of each individual in all dimensions: physical, psychological, social, family, and spiritual 2. Promote quality of life, defined by the patient, by providing relief from symptoms of pain and minimizing secondary effects 3. Ensure the right of the patient to have access to pain medication and treatments that minimize pain and trauma 4. Know and use treatments that minimize pain and trauma (eg, dressings that will not adhere to the wound bed or damage the periwound skin) 5. Always take time to assess the patient's pain and engage the patient in treatment decisions and process. Anxiety, depression, and pain. The relationship between depression and pain is complex. Depressed patients generally do not have good control of persistent pain until their depression is adequately treated. However, treating the depression does not eliminate the need to treat pain. Because tricyclic antidepressants (nortriptyline) also may be useful in treating neuropathic pain, these agents may be useful for neuropathic pain in the presence of depression.16 Anxiety can increase a pain response, and the combination of an anxiolytic and an opioid may improve pain control.16 In the elderly, the risk of confusion, orthostatic hypotension, and falls may be increased by the use of anxiolytics and/or antidepressants with opioids. These combinations should generally be used carefully in the older patient.16 The patient should not to focus exclusively on the pain - rather, function or other goals (for example, improving comfort to a level that allows the patient to get to the bedside commode or to the bathroom) should be emphasized.16 Non-pharmacological management of pain. Patient education is vital. In fact, patient education programs alone, with or without learning coping strategies, significantly improve overall pain management.43-45 Participation in therapeutic exercise programs has been used to treat persistent pain.46 Additional non-pharmacologic interventions include cold therapy (which can suppress tissue damage) as well as warmth, transcutaneous electrical nerve stimulation, and acupuncture. All of these modalities result in the release of endogenous opioids. Although many patients may benefit, others find allodynia may actually be aggravated by various alternate stimuli. The gate control theory of Melzack and Wall47 postulates that alternate nerve pathway stimulation may interfere with and reduce the perception of painful stimuli. Relaxation techniques, biofeedback, or hypnosis also may be useful. Physical therapy and occupational therapy can be crucial and offer a wide range of options, such as the use of braces or splints, changes in biomechanics, and exercise. All have been demonstrated to relieve pain. Nerve blocks and tumor site radiation also can be helpful in certain circumstances.4 Increasing numbers of patients are seeking alternative therapies such as homeopathy, naturopathy, and spiritual healing. These may be of benefit to some patients, but until further rigorous studies are completed, making specific recommendations about long-term use of these therapies is premature. Considerations for Local Wound Care An international survey from Europe and North America published by Moffatt, Franks, and Hollinworth40 concluded: 1. Dressing removal is considered to be the time of most pain 2. Dried-out dressings and adherent products are most likely to cause pain and trauma at dressing changes 3. Products designed to be nontraumatic are most frequently used to prevent tissue trauma 4. Gauze is most likely to cause pain. New products such as soft silicone dressings, hydrogels, hydrofibers, and alginates are least likely to cause pain 5. Awareness of product range and ability for dressing selection is highly variable between countries 6. Use of valid assessment tools is considered a low priority in assessment; greater reliance is placed on body language and nonverbal cues. Local wound care practices can have a significant effect on the management of pain. These can be both pain-causing and pain-relieving. Debridement. Wound debridement can be achieved through different means: surgical, autolytic, enzymatic, and mechanical.48 A number of factors come into play when choosing an appropriate debridement method (see Table 5). Each method can have a negative or positive impact on wound pain. The more aggressive the debridement method (eg, surgical and mechanical), the potentially more painful it is for the patient. In the presence of neuropathy, surgical debridement may be painless unless deeper structures (ie, bone) are disrupted. Quickness to debride should not be at the expense of pain. Enzymatic or autolytic debridement is slower but generally less painful; autolytic is mostly pain free. Caregivers should choose a debridement method that removes necrotic tissue efficiently and painlessly. For surgical debridement, topical local anesthetics such as 4% topical lidocaine may be helpful when applied 15 to 30 minutes before the procedure. For deeper debridement, injected local aesthetics should be used. Even though spinal cord injured patients are often insensate in the area to be debrided, injected local aesthetics should be used to avoid autonomic dysreflexia, which can cause catastrophic elevations in blood pressure. If oral pain medication is used, the agents should be administered 30 to 90 minutes before the procedure to obtain therapeutic effect. Non-pharmacologic interventions are also important for debridement. Interventions include proper positioning, provision of prior procedural and sensory information, use of a pain intensity scale, clarifying roles and responsibilities for pain management, and helping patients develop a strategy for pain control before debridement.48 Pain control strategies include guided imagery, talking to a supportive person, warm sheets, and the ability to call time out when pain gets to a predetermined level. Superficial infection/inflammation. Infection and inflammation can be painful.49 Prevention of infection/inflammation is the cornerstone with respect to avoiding pain but such prevention is not always possible. Indeed, the patient with a chronic wound often presents with pain. Treatment to reduce or eliminate any infection or inflammation will often improve the associated pain. Superficial infections may be treated with topical antimicrobials (see Table 6) while deeper infections require systemic agents.50 Topical treatment. Deciding on a treatment regimen should include awareness of pain and other patient-centered factors. When choosing topical antimicrobials, the clinician should avoid topical sensitizers, agents that might be used systemically, and those that are toxic to granulation tissue. Many topical preparations, both pharmacological and non-pharmacological (eg, antibacterial dressings) treat both infection and inflammation; however, acute inflammation is an important phase in healing and any treatment chosen should be used only in cases of chronic inflammation.51,52 Dressings that contain silver may have both effects.53 Many of these preparations can be soothing or cooling (eg, ointments/gels) or can create an appropriate environment to reduce/prevent pain (eg, moist dressings). Effective, pain-free patient care can be delivered by choosing a regimen which treats/prevents any infection or inflammation without traumatizing the wound or its surrounding periwound area. Moist interactive healing. The concept of moist wound healing is not new. Winter54 first published his findings from an animal model 40 years ago. He showed faster healing was achieved when the wound was covered by a plastic cover. A moist environment was created that enabled more efficacious cell migration, leading to faster wound closure. Winter and others went on to study this phenomenon in humans and demonstrated not only faster healing but also better tissue quality (less scarring56 and pain-free healing). Pain reduction was attributed to bathing the exposed nerve ending in fluid, preventing dehydration of the nerve receptors. The moist interactive dressings of today are based on the same principle. By creating a moist environment, they aid healing and soothe nerve endings, minimizing or eliminating wound pain. Creating and maintaining a moist environment is, therefore, important with regard to reducing or eliminating wound pain. However, a dry environment is not the only dressing factor that can lead to pain. Other dressing-related factors that can cause pain include the dressing absorbency mechanism; dressing adherence; friction between dressing surface and wound bed; dressing/granulation tissue integration; and the presence of allergens. Moisture balance (dressing performance). The way a dressing absorbs and manages exudate not only affects the physical performance of the material but also impacts wound pain. A dressing will adhere to the wound if it absorbs too aggressively or if the primary dressing allows strikethrough, adhering to secondary layers or regimens. Adhesion of primary and secondary products can result in the accidental traumatic removal of the primary contact layer and cause damage (and pain) to the wound bed. Fibrous products (eg, alginates and hydrofibers) are excellent primary contact layers. They are gel-formers; as a result, they bathe the wound bed in a soft soothing gel. This allows nontraumatic removal and generally provides pain relief. Some dressings are abrasive and can cause friction or adherence to the wound surface (eg, some gauze-based products). This can be avoided by using appropriate dressings (eg, gels/foams) or utilizing a nontraumatic wound contact layer (eg, soft silicone dressings). Research has shown these products to be relatively atraumatic upon removal.57 Adhesive dressings, as the name suggests, can be traumatic to both the wound bed and the periwound area. Films and hydrocolloids should be removed with care as recommended by the manufacturer's instructions. Hydrocolloids are generally nonadherent to the wound bed because they form a soft, conforming gel in the presence of exudate.58 Care should be taken upon removal, however, to ensure no skin stripping of the periwound area.59 Again, appropriate use will prevent damage and pain and provide an effective moist wound environment.60 Care also should be exercised regarding the choice of dressing or other topical treatment regarding allergens that can cause uncomfortable or painful inflammation (ie, allergic response). Use of products with a high sensitization potential (eg, neomycin, Bacitracin, lanolin, and perfumes) in patients with leg ulcers should be avoided.61 Wound pain as a result of inappropriate local wound care generally can be corrected. A well-devised local wound care regimen with the appropriate elements (dressings for moisture balance, bacterial balance/controlled inflammation, and autolytic debridement where appropriate should be patient, wound, and disease specific (see Table 7). Conclusion Pain is often neglected because no simple diagnostic test exists to measure it. Quite simply, "Pain is what the patient says it is." Too often clinicians ignore pain because it is not easy to measure, yet unrelieved pain may seriously hamper efforts to heal chronic wounds. A paradigm that integrates pain management into an approach to wound bed management provides the clinician with a framework for improved care. An approach to chronic wound pain management that treats the cause and addresses local wound factors may lead to improved outcomes as patients may be more adherent to optimal care plans. A patient-centered regimen ensures appropriate care in a reduced pain environment (see Table 8). - OWM